Gene expression modifications in Wharton's Jelly mesenchymal stem cells promoted by prolonged in vitro culturing

Background: It has been demonstrated that the umbilical cord matrix, represented by the Wharton's Jelly (WJ), contains a great number of mesenchymal stem cells (MSCs), characterized by the expression of specific MSCs markers, shared by both human and animal models. The easy access to massive WJ amount makes it an attractive source of MSCs for cell-based therapies. However, as in other stem cell models, a deeper investigation of WJ-derived MSCs (WJ-MSCs) biological properties, probably modulated by their prolonged expansion and fast growth abilities, is required before their use in clinical settings. In this context, in order to analyze specific gene expression modifications occurring in WJ-MSCs, along with their culture prolongation, we investigated the transcriptomic profiles of WJ-MSCs after 4 and 12 passages of in vitro expansion by microarray analysis. Results: Hierarchical clustering analysis of the data set originated from a total of 6 experiments revealed that in vitro expansion of WJ-MSCs up to 12 passages promote selective over-expression of 157 genes and down-regulation of 440 genes compared to the 4th passage. IPA software analysis of the biological functions related to the identified sets of genes disclosed several transcripts related to inflammatory and cell stress response, cell proliferation and maturation, and apoptosis. Conclusions: Taken together, these modifications may lead to an impairment of both cell expansion ability and resistance to apoptosis, two hallmarks of aging cells. In conclusion, results provided by the present study suggest the need to develop novel culture protocols able to preserve stem cell plasticity.